1. Field of the Invention
The present invention relates to glycuronamides, glycosides and orthoester glycosides of fluoxetine and analogs and their use in therapy.
2. Related Art
Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor and is sold as an antidepressant and for the treatment of eating disorders. Fluoxetine hydrochloride is also reported to be useful for the treatment of obsessive-compulsive disorder, bulimia, pain, obsessive-compulsive personality disorder, post-traumatic stress disorder, hypertension, atherosclerosis, anxiety, anorexia nervosa, panic, social phobia, stuttering, sleep disorders, chronic fatigue, Alzheimer's disease, alcohol abuse, appetite disorders, weight loss, agoraphobia, amnesia, smoking cessation, nicotine withdrawal syndrome symptoms, disturbances of mood and/or appetite associated with pre-menstrual syndrome, depressed mood and/or carbohydrate craving associated with pre-menstrual syndrome, disturbances of mood, disturbances of appetite or disturbances which contribute to recidivism associated with nicotine withdrawal, circadian rhythm disorder, borderline personality disorder, hypochondriasis, pre-menstrual syndrome (PMS), late luteal phase dysphoric disorder, pre-menstrual dysphoric disorder, trichotillomania, symptoms following discontinuation of antidepressants, aggressive/intermittent explosive disorder, compulsive gambling, compulsive spending, compulsive sex, psychoactive substance use disorder, schizophrenia, premature ejaculation, or psychiatric symptoms selected from the group consisting of stress, worry, anger, rejection sensitivity, and lack of mental or physical energy without an increase in nausea. See U.S. Pat. Nos. 4,314,018, 4,626,549, 5,985,322 and 5,910,319.
Wirth, D.D. et al., J. Pharm. Sci. 87:31–39 (1998), discloses that generic formulations of fluoxetine hydrochloride comprise lactose and are inherently less stable than formulations containing starch due to the Maillard reaction between the fluoxetine and lactose. N-formylfluoxetine was identified as the major product.